Oxygen affinity synthesis and stability of abnormal hemoglobins will be measured; relations between structure and function will be examined. The process of hemoglobin denaturation by heat, oxidants and isopropanol will be investigated with particular attention to generation of "activated" oxygen, and membrane damage in intact red cells. Correlations will be made between the properties of purified abnormal hemoglobins and the clinical status of the patients from whom the samples were obtained. The quantity of abnormal hemoglobin in red cells and interaction with the environment are suggested as important determinants of morbidity. Adaptation to chronic tissue hypexia, produced by quantitative or qualitative abnormality of hemoglobin, will be studied by physiological and biochemical methods.